PSA, or Prostate Specific Antigen, is a protein secreted by normal prostate tissue glands, primarily into the ejaculate fluid, with a small amount measured in the blood.  Any inflammatory process, acute injury, significant benign enlargement, or prostate cancer, may elevate the PSA. Primary care physicians usually draw the PSA with routine blood tests at the time of annual physical examinations, starting at age 50 for most men, or at age 40 for patients at higher risk. The higher risk patients include men with a family history for prostate cancer or African-Americans. This screening improves survival if the tumor is found and treated early.

These are normal PSA values based on age:

Age	Normal PSA ng/ml
40-49	less than 2.5
50-59	less than 3.5
60-69	less than 4.5
70-79	less than 6.5

     
Factors that Affect the PSA Test

• The digital rectal examination (DRE) is an important part of an annual physical exam, even in the PSA era.  A prostate nodule or an irregular-feeling prostate may indicate an early prostate cancer despite a normal PSA test.   A vigorous DRE, such as a prostate massage in evaluating for prostate inflammation, may also falsely elevate the PSA.
• Recent sexual activity or a cytoscopy test may cause PSA levels to rise.
• The medication finasteride (Proscar), used to prevent further enlargement of the prostate gland in men with benign prostatic hypertrophy (BPH), can lower PSA levels by 50%. Once a patient starts Proscar, a PSA should be drawn to establish a new baseline.  Whenever future PSA's are done, this new baseline is used for reference.
• Rough handling, contamination, or inadequate refrigeration of the blood sample can cause inaccurate test results. 
• Men older than 80 have a high likelihood of slow-growing prostate cancer. Older men also have medical problems like heart disease, diabetes, neurologic conditions, other cancers. In those men, routine screening PSA testing is not recommended.  PSA screening is also not recommended in any patient with major medical problems and a life expectancy of less than 10 years.

Preparing for the PSA test

• Avoid sexual activity 2 to 3 days prior to testing.
• Wait several weeks after having a cytoscopy, a test to evaluate the urethra and bladder.
• Wait until a urinary tract infection or prostatitis has cleared up.

Interpreting Abnormal PSA Results 

The risk of prostate cancer increases with higher PSA values, with about a 25% likelihood of prostate cancer with an elevated test.  Thus, most men with an abnormal PSA test will not have prostate cancer.  While the classic prostate cancer was a hard or nodular prostate, the most commonly diagnosed prostate cancer today is with an abnormal PSA test and normal feeling prostate on rectal examination. 

Thus, the only way to determine this is by performing a prostate biopsy, taking tiny samples with a spring-loaded needle from the prostate through the rectal wall, often using an ultrasound probe (TRUS or trans-rectal ultrasound) to see the prostate tissue.  Patients take an antibiotic starting the day before the procedure to minimize infection, and stop taking aspirin or non-steroidal anti-inflammatory medications, like ibuprofen (Motrin or Advil), 7-10 days prior to the procedure to minimize bleeding problems.  The biopsy takes less than 5 minutes to perform, and patients may hear a snapping sound or feel a pinch from the biopsy needle.  Usually at least 8 biopsies are taken.  A local anesthetic may be injected, particularly if more biopsies are needed.

The PSA slope refers to the change in PSA over a sustained period of time, years rather than months.  While an individual abnormal PSA may prompt concern, many of these situations are transient, or temporary, elevations from benign conditions, where the PSA will return to baseline.  But when the PSA steadily rises more than 0.8/year over 2 consecutive years, then there is greater likelihood of prostate cancer.  So it is important to obtain a series of PSA values, far enough apart, to demonstrate a significant trend upwards, even within the normal range. For instance, a 52 year old man with PSA rising from 1.1 to 1.8 to 2.7 over 2 years would be worrisome, even though his highest PSA is still less than 3.5, the normal for his age group. 

Free-PSA is the unbound portion of the total PSA, and is more associated with benign disease.  So in patients with an elevated total PSA, when the free-PSA fraction is >25%, the risk of prostate cancer is low (about 8%).  But if the free-PSA fraction is <10%, then the risk is high (about 56%).  For most patients, the free-PSA fraction will be in between 10 and 24%, where the risk is intermediate at 25%.  The free-PSA is most useful in deciding whether or not to rebiopsy a patient with abnormal PSA following previous negative biopsy.

HGPIN

PIN, or Prostatic Intra-epithelial Neoplasia, is a term used to describe abnormal cell structures in prostate glands.  Years ago, when it was first described, it was thought that these atypical areas were all pre-malignant, eventually becoming invasive prostate cancer. The current thinking is that these are not all pre-cancerous, but depending on the type, they may be a warning of nearby or future cancer. The low-grade type (Type1 PIN) behaves like benign (normal) glands, while the high-grade types (Types 2, 3 or HGPIN, High-Grade PIN) carry a 50% likelihood of the presence of, or future development of prostate cancer.  In patients undergoing radical prostatectomy for prostate cancer, there was a very high (up to 85%) incidence of HGPIN within the remainder of the gland. Thus, the more extensive the HGPIN is found on individual biopsies, or the more biopsies that show even tiny focal areas of HGPIN, the more concern there is about a lurking prostate cancer, which may prompt additional biopsies.